Abstract This NCCU-UNC collaboration seeks to evaluate novel approaches to reduce disparities in and the morbidity and mortality attributable to high-grade precancerous lesions (CIN2+) and invasive cervical cancer by (1) improving the accessibility of primary screening by testing urine samples rather than physician-collected samples, (2) increasing adherence to follow-up of abnormal screening results, and (3) reducing unnecessary referral to follow-up screening among women with abnormal results. We will evaluate these approaches by completing the following specific aims: Aim 1: Assess the validity of testing for oncogenic human papillomavirus (HPV) in urine compared to physician-collected cervical samples for the detection of high-grade cervical intra-epithelial neoplasia (CIN2+). We will: (1) Conduct HPV testing in urine and cervical samples from 160 patients attending the UNC colposcopy clinic and from 250 women with cytology normal/ HPV positive results at UNC primary screening clinics, followed by colposcopy with directed biopsy, (2) Calculate the validity (sensitivity, specificity, positive and negative predictive values) of the new urine diagnostic test for detection of biopsy-confirmed CIN-2+. Aim 2: Examine new approaches to improve patient adherence to follow-up colposcopy screening ? needed for the appropriate referral to treatment and prevention of invasive cancer ? by (a) assessing perceptions of urine HPV-testing versus clinic-based Pap or HPV/Pap co-testing, and (b) developing the content and protocol for a text-message-based intervention to increase colposcopy attendance, to be tested in a future efficacy trial. 2a. We will conduct semi-structured interviews with 15 women undergoing cervical cancer screening to assess their understanding of and attitudes towards HPV urine testing compared to in-clinic Pap/HPV co-testing. 2b: We will conduct a target audience assessment of women referred to colposcopy following an abnormal screening result, then use this assessment and existing evidence to develop and pilot test the content of a proposed tailored text-message reminder intervention designed to improve patient follow-up to colposcopy. Aim 3: Investigate the clinical performance of testing for the E6 protein of HPV types 16 and 18 for the detection of CIN-2+ among HPV-positive women in order to assess its potential for use in triage to colposcopy. We will (1) Complete HPV E6 test testing on urine and cervical samples collected in Aim 1 from patients with cytology negative/HPV-positive screening results: 250 primary screening patients and 40 colposcopy patients; (2) Calculate the validity (sensitivity, specificity, positive and negative predictive values) for biopsy-confirmed CIN-2+ of HPV E6 triage testing among HPV-positive women with normal cytology. The successful completion of this project will provide valuable insight into new approaches to improve effectiveness and reduce the resource burden of cervical cancer screening, as well as develop the research skills of the NCCU collaborators and provide a basis for future successful proposals to conduct larger trials.